Crystal structure of human intrinsic factor: cobalamin complex at 2.6-A resolution

Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17311-6. doi: 10.1073/pnas.0703228104. Epub 2007 Oct 22.

Abstract

The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-A resolution. The overall fold of the molecule is that of an alpha(6)/alpha(6) barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an alpha- and a beta-domain and one Cbl, and two truncated molecules with only an alpha- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co(2+) is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Intrinsic Factor / chemistry*
  • Intrinsic Factor / genetics
  • Intrinsic Factor / metabolism*
  • Models, Molecular
  • Oncogene Protein v-cbl / chemistry
  • Oncogene Protein v-cbl / metabolism
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Static Electricity
  • Structural Homology, Protein
  • Vitamin B 12 / chemistry*
  • Vitamin B 12 / metabolism*

Substances

  • Oncogene Protein v-cbl
  • Intrinsic Factor
  • Vitamin B 12